A peri‐operative statin update for non‐cardiac surgery. Part II: Statin therapy for vascular surgery and peri‐operative statin trial design

Abstract

SummaryThis is the second of two review articles evaluating peri-operative statin therapy. In surgical patients, the utility of peri-operative statin therapy is strongly suggested by retrospective studies, although it is probably overestimated, as important confounding factors have not been controlled for and hence the literature is considered to be currently inconclusive.This review examines the potential mechanisms and indications for peri-operative statin protection, the efficacy of acute peri-operative beta-blockade in addition to statin therapy, the effect of peri-operative statin therapy withdrawal and the implications of comorbidities associated with peri-operative cardiovascular risk on statin therapy. Recommendations concerning appropriate dosing, duration, therapeutic targets and necessary investigations when prescribing peri-operative statins are made. Peri-operative study design recommendations are suggested, so that future meta-analyses may be more informative. Recommendations are made regarding retrospective reporting of statin studies to minimise the bias inherent in a number of the current retrospective studies on this subject. This is the second of two review articles evaluating perioperative statin therapy. In the first review article, the cellular and metabolic responses to statin therapy were examined. The duration and timing of statin therapy and therapeutic targets in patients with stable and unstable coronary artery disease (CAD) were presented [1]. In this review the evidence regarding the utility and safety of peri-operative statin therapy is examined. The indications for peri-operative statin therapy, the role of acute betablockade, the implications of withdrawal of statin therapy and comorbidities associated with peri-operative cardiac events are discussed. The potential role of intensive therapy in vascular surgical patients is considered. Finally, recommendations for peri-operative statin therapy and clinical trials are made based on the findings reported in these two reviews. Peri-operative evidence of cardiovascular protection by statinsInflammation as a determinant of adverse peri-operative cardiovascular events surgery Approximately half of peri-operative myocardial infarctions occur as a result of vulnerable plaque rupture in coronary arteries which are not critically stenosed [2,3]. Patients who have myocardial infarction or death following vascular surgery have an increased coronary plaque load, as documented by more diseased coronary vessels, more irregular lesions, more coronary segments with irregular lumens and more collaterisation [4].Surgery is associated with a systemic inflammatory response [5]. Aortic surgery initiates a systemic inflammatory response secondary to bowel manipulation and

Quantifying and communicating peri-operative risk

“…Why not assume the worst and instigate protective measures anyway? Over the last decade, statins have been investigated extensively for their potential multimodal effects in modifying a number of aspects of peri‐operative morbidity and mortality . Possible pleiotropic effects of statin therapy are reduction of myocardial infarction and stroke, prevention of atrial fibrillation, improvement of vascular draft survival, protection from renal insufficiency, and inhibition of malignant cell growth .…”

Preoperative optimization

“…The Decrease IV trial [37] demonstrated an advantage in preoperative statin therapy in terms of outcome with a number needed to treat of 12.5. The disadvantages of the drug side-effects of liver dysfunction and rhabdomyolysis appear minimal when compared with the advantages [45] demonstrated that perioperative statin use is a cost-effective use of statins due to avoidance of cardiovascular complications. In vascular patients particularly, preoperative statin therapy has been demonstrated to reduce resource utilization and clinical outcomes [45].…”

“…The disadvantages of the drug side-effects of liver dysfunction and rhabdomyolysis appear minimal when compared with the advantages [45] demonstrated that perioperative statin use is a cost-effective use of statins due to avoidance of cardiovascular complications. In vascular patients particularly, preoperative statin therapy has been demonstrated to reduce resource utilization and clinical outcomes [45]. Recommendations advise statin use in the secondary prevention for patients with coronary artery disease, stroke and peripheral vascular disease, yet only 32% patients in the POISE trial [48] were being treated.…”

Additional advantages of pre‐operative statin use in patients undergoing non‐cardiac vascular surgery

“…Biccard evaluated the benefits associated with pre‐operative statin use in patients undergoing non‐cardiac vascular surgery [1]. A few additional comments may be of interest:…”